Pre-angioplasty serration of atherosclerotic plaque enabling low-pressure balloon angioplasty and avoidance of stenting

ABSTRACT

A device and method for intravascular treatment of atherosclerotic plaque prior to balloon angioplasty which microperforates the plaque with small sharp spikes acting as serrations for forming cleavage lines or planes in the plaque. The spikes may also be used to transport medication into the plaque. The plaque preparation treatment enables subsequent angioplasty to be performed at low balloon pressures of about 4 atmospheres or less, reduces dissections, and avoids injury to the arterial wall. The subsequent angioplasty may be performed with a drug-eluting balloon (DEB) or drug-coated balloon (DCB). The pre-angioplasty perforation procedure enables more drug to be absorbed during DEB or DCB angioplasty, and makes the need for a stent less likely. Alternatively, any local incidence of plaque dissection after balloon angioplasty may be treated by applying a thin, ring-shaped tack at the dissection site only, rather than applying a stent over the overall plaque site.

This U.S. patent application is a continuation-in-part of co-pendingU.S. patent application Ser. No. 12/408,035 of the same inventors, filedMar. 20, 2009, which claimed priority to the filing date of U.S.Provisional Appln. 61/038,477, filed on Mar. 21, 2008.

TECHNICAL FIELD

The present invention is directed to a device and method for openingblood vessels in the body occluded by atherosclerotic plaque bypre-angioplasty serration and dilatation of the plaque.

BACKGROUND

Atherosclerotic occlusive disease is the primary cause of stroke, heartattack, limb loss, and death in the US and the industrialized world.Atherosclerotic plaque forms a hard layer along the wall of an arteryand is comprised of calcium, cholesterol, compacted thrombus andcellular debris. As the atherosclerotic disease progresses, the bloodsupply intended to pass through a specific blood vessel is diminished oreven prevented by the occlusive process. One of the most widely utilizedmethods of treating clinically significant atherosclerotic plaque isballoon angioplasty.

Balloon angioplasty is an accepted and common method of opening blockedor narrowed blood vessels in every vascular bed in the body. Balloonangioplasty is performed with a balloon angioplasty catheter. Theballoon angioplasty catheter consists of a cigar shaped, cylindricalballoon attached to a catheter. The balloon angioplasty catheter isplaced into the artery from a remote access site that is created eitherpercutaneously or through open exposure of the artery. The catheter ispassed along the inside of the blood vessel over a wire that guides theway of the catheter. The portion of the catheter with the balloonattached is placed at the location of the atherosclerotic plaque thatrequires treatment. The balloon is inflated to a size that is consistentwith the original diameter of the artery prior to developing occlusivedisease.

When the balloon is inflated, the plaque is stretched, compressed,fractured, and/or broken, depending on its composition, location, andthe amount of pressure exerted by the balloon. The plaque isheterogeneous and may be soft in some areas or hard in others causingunpredictable cleavage planes to form under standard balloonangioplasty. The basic mechanism of balloon angioplasty relies on acombination of actions caused by the balloon exerting pressure on theatherosclerotic plaque, including; compression of the plaque and thefracture of the hard, circumferentially calcified portion of the plaque.Balloon angioplasty causes plaque disruption and sometimes it causesarterial injury at the angioplasty site. Balloon angioplasty is oftenperformed at high inflation pressures, in excess of 4 atmospheres, verycommonly at 8 atm and sometimes up to 22 atm. These high pressurescontribute to the unpredictable results of balloon angioplasty.

When the angioplasty balloon is expanded with enough pressure to open ahard plaque, dissection often occurs; the hardened areas becomedisrupted and partially separated from the arterial wall and are proneto lifting up as flaps or chunks. The higher the pressure of balloonangioplasty and the more rapidly the pressure reaches a high level, themore often it produces dissection. The random cleavage planes that arecreated by the dissection depend upon the composition of the plaque andthe pressure exerted upon it. The cleavage planes tend to be wandering,longitudinal lines. The depth of the cleavage planes or fractures thatare created by balloon angioplasty varies significantly and may besuperficial or may be deep and extend all the way to the media of thearterial wall. To the extent that the cleavage plane goes across theline of flow, that is perpendicular or diagonal to the axial directionof the vessel, there is the potential for partial or complete lifting ofa flap. When a flap of fractured plaque has lifted, it may cause acuteocclusion or blockage of blood flow, or leave a significant residualstenosis, or may extend to create a larger flap.

Frequently, a segment of the plaque is more resistant to dilatation thanthe remainder of the plaque. When this occurs, greater pressure pumpedinto the balloon results in full dilatation of the balloon to itsintended size. The balloon is deflated and removed and the arterysegment is reexamined, usually using angiography. The process of balloonangioplasty is one of uncontrolled plaque disruption. The lumen of theblood vessel at the site of treatment is usually somewhat larger, butnot always and not reliably. Some of the cleavage planes created byfracture of the plaque with balloon angioplasty form dissection. Adissection occurs when a portion of the plaque is lifted away from theartery and is not fully adherent and may be mobile or loose. The plaquethat has been disrupted by dissection protrudes into the flowstream. Ifthe plaque lifts completely in the direction of blood flow, it mayimpede flow or cause acute occlusion of the blood vessel.

The dissection of plaque after balloon angioplasty is treated to preventocclusion and to resolve residual stenosis. A common practice has beento place a retaining structure, such as a rigid or semi-rigid tubularstent, to hold the artery open after angioplasty and retain thedissected plaque material back against the wall of the blood vessel tokeep an adequate lumen open for blood flow. The clinical management ofdissection or residual narrowing after balloon angioplasty is currentlyaddressed through the development of increasingly complex stentstructures. However, there has been substantial clinical evidence ofdisadvantages with using stents, including body rejection of a largemass of foreign material, and the emplacement of extensive surface areaof a stent that may become sites for re-accumulation of plaque orre-stenosis due to smooth muscle cell growth and intimal hyperplasia.

In juxtaposition to lesions that may develop significant dissectionafter balloon angioplasty, a substantial proportion of patients do notsustain major dissections as a result of balloon angioplasty. This seemsto depend on several factors, including; the location and morphology ofthe lesion, and the pressure required to dilate the lesion duringballoon angioplasty, but is also to some extent unpredictable. Thissituation does not require a stent. When post-angioplasty blood vesselsshow no sign or minimal sign of dissection and are left to heal on theirown, i.e., when no stent is implanted, especially in the iliac andfemoro-popliteal arteries, the rate of acute re-occlusion is low. Thelong-term success of balloon angioplasty alone in many cases may producethe same or better long-term results than if a stent was emplaced.Balloon angioplasty without stenting therefore remains one of the mostcommon endovascular procedures in arteries and veins through out thebody and one of the most cost effective.

When it is deemed necessary that a stent is required at a given site ofplaque buildup, it is highly desirable to have the ability to fullydilate the stent within the lesion. This is a problem that has been thefocus of intensive investigation and is due to the fact that somelesions are so recalcitrant to dilatation, that they cannot be dilatedeven at very high pressures.

Accordingly, it is deemed highly desirable to dilate plaque material soas to create a smooth post-angioplasty surface without elevated flaps ordissection, and to reduce the need for post-angioplasty stent placement.It is further desirable to provide a method of dilatation that permitsbetter expansion of the lumen, such that if a stent is required, itallows the stent to be fully opened. In cases where local sites ofpost-angioplasty dissections or non-smooth lumen walls presentthemselves, it may be desirable to implant a retaining structure otherthan a stent which offers a minimal surface footprint and exerts lowlateral pressures against the post-angioplasty surface.

SUMMARY OF INVENTION

To overcome the problems and disadvantages of prior practices ofdilating plaque material in blood vessels through balloon angioplastyand with or without the use of post-angioplasty stent emplacement, thepresent invention employs an intravascular device for pre-angioplastytreatment carrying rows or patterns of small sharp spikes that areactuated by an expansion balloon or other apparatus to pierce theluminal surface of atherosclerotic plaque with lines or patterns ofmicroperforations which act as serrations for forming cleavage lines,expansion lines, or planes in the plaque as a preparation prior toballoon angioplasty. When using a balloon actuated mechanism to pressthe spikes into the plaque to create the microperforations, expansionpressures of a full range may be used, from less than 2 atm to more than10 atm. This pressure range may only be necessary for the purpose ofintroducing the spike elements into hardened calcified plaque. When aballoon actuated mechanism is used to create the microperforations, theblood vessel is only being prepared and is not being fully dilated toits intended diameter. The diameter of the artery is much larger thanthe fully expanded diameter of the spike device. Therefore the wall ofthe artery does not experience high pressure when the spike device isballoon actuated avoiding the danger identified in high pressure balloonangioplasty.

After preparation of the plaque with the microperforation and serrationprocedure, the plaque can be compressed and the artery lumen safely andaccurately dilated and stretched, using low pressure balloonangioplasty, to its intended diameter without creating numerous andsubstantial dissections and elevated flaps. The microperforation andserration enable the plaque to be dilated more evenly and smoothly andavoid forming random cracks that may lead to dissection and residualstenosis. The plaque, after it has been pre-treated withmicroperforation and serration, may also be dilated with lower pressurethan that which is used in standard balloon angioplasty. The lowerintra-balloon pressure (e.g., less than or equal to 4 atm and very oftenless than or equal to 2 atm) causes less disruption of the plaque, fewerdissections, and less injury to the artery wall. This “low pressure” or“minimal injury” angioplasty is less likely to cause the biologicalreaction that often follows balloon angioplasty with neointimalhyperplasia or smooth muscle cell replication.

In addition, microperforation and serration permits the plaque to expandwith less fracturing or disruption of the plaque during balloonangioplasty. By preparing the plaque using microperforations and thenperforming a balloon angioplasty at low pressure, the number andseverity of dissections is reduced. This decreases the need for stentplacement to be used to treat dissection or residual stenosis afterballoon angioplasty. The subsequent balloon angioplasty may be performedat low balloon pressures of about 4 atmospheres or less due topreparation of the plaque with perforations, so as to avoid injury tothe arterial wall. By performing plaque preparation and then lowpressure angioplasty, there is less likelihood of a dissection occurringdeeply and exposing the media layer of the artery. Exposure of thisartery stimulates thrombus formation by collagen exposure and alsostimulates smooth muscle cell growth which later causes neointimalhyperplastic occlusion of the artery. This decrease in number and alsodecrease in severity of dissection is a key differentiating factor incomparison to cutting or scoring devices.

Preferred embodiments of the perforation and serration device forpre-angioplasty treatment include three varying methods for spikedeployment, through mechanical (or electromechanical or microelectromechanical), balloon, and balloon-assist deployment. In amechanical (or electromechanical or micro electromechanical) deploymentmethod, lines or patterns of spikes protrude from a carrier surface orare extracted from the core of a catheter used for remote delivery. In aballoon deployment method, the spikes are mounted on an expandableballoon (similar to those used in angioplasty). In a balloon-assistmethod, the spikes are mounted on a carrier surface, and the carriersurface is pushed against the plaque under the expansion force of aballoon. The balloon in this method is used as means to stabilize thespikes within the artery and assist in pushing the spikes into theartery wall. In this method one may or may not use the device to performarterial expansion without a separate balloon angioplasty procedure.Related methods are provided for a insertion of the spikes in acompressed state into the blood vessel and expanding them to theintended shape for plaque microperforation and serration, and thenre-seating the spikes for withdrawal. Several variations for spikemounting and delivery, and variations for spike cross-sectional profilesand for placement in lines and other patterns are further disclosed.

Preferred embodiments include a delivery device in which spikes areformed like polymer gum drops on a carrier ribbon or strip which areattached on the surface of an expansion balloon that is folded to acompact state for delivery. Another embodiment has spikes shaped assharp pins carried on mesh bases and folded into flaps of an expansionballoon. Another embodiment of the delivery device has spikes that aredeployed from and retracted back into a mechanical carrier. Anotherembodiment of the delivery device has spikes carried or projectable fromthe surface of a catheter carrier and an external multi-lobed balloonfor pressing the spikes in circumferential sections against the plaque.Yet another embodiment has spikes carried on an accordion-likestructure. The spikes may also be carried on ribbons strips of a slittedmetal tube which are biased by shape memory outwardly toward thearterial wall. The spikes may be carried on a button structure forattachment to a carrier, or may be carried on a stretchable meshstructure over an expansion balloon. The spikes may be arranged invarious patterns on the delivery device depending on the cleavage planesdesired to be formed in the plaque.

The pre-angioplasty treatment of a plaque site may also be combinedinstead with drug-eluting balloon (DEB) angioplasty or drug-coatedballoon (DCB) angioplasty. Due to the various applications of balloonangioplasty, there are a variety of medications that may be used, suchas: plaque-reducing medication, thrombus inhibiting medication,inhibitors of cell growth, other biologically active treatments, andstem cell delivery. The intended effect is to have the medication takenup by or adhered to the plaque and/or wall of the diseased artery at thetime of balloon angioplasty. The preparation of the plaque and thecreation of microperforations enhances the uptake and biologicalactivity of the medication. The creation of new plaque surface area inthe depths of each of the microperforations, and also the location ofthe plaque that has been exposed, in the top layer of the plaque withoutexposing the medial layer, is further facilitative of the biologicalactivity of the medication.

Other variations for the spike device include having drug-coated tips,or an internal drug-containing reservoir where each spike behaves like asyringe, or where the spikes are medication-eluting or bearing and aredetached and left in place after perforation of the plaque. In thelatter variation, if the spikes are made of bio-degrading orbio-absorbable material, over time the left-behind spikes are degradedor absorbed and leave behind only the perforation holes. Due to thegreater penetration and surface area contacted, the left behind spikeswould provide greater infusion of medication into the diseased area.Detachable spikes may also be biased to restrain the area of plaquearound the tips acting like a regional staple that tacks the plaqueagainst the wall.

Another variation for the pre-angioplasty treatment is the use of aballoon-restricting mesh over the expansion balloon for restricting itsmaximum expansion diameter so that it is less than the blood vesseldiameter. The mesh minimizes the potential of the balloon to expandbeyond the stenosis site into an hour-glass shape, and also limits theamount of pressure that is delivered to the plaque by limiting theballoon to a defined radial expansion. The mesh structure can be includespike buttons or by milled (through grinding, laser cutting, metalextrusion, photolithography, or other means) to form sections withheight variations that act as microperforations.

As an alternative to stent emplacement, in cases where one or more localsites of plaque dissections or flaps present themselves after balloonangioplasty, a thin, ring-shaped tack device may be placed at only thelocation of each specific problem site, so that the amount of foreignmaterial emplaced as a retaining structure in the blood vessel can beminimized and exert only low lateral pressures against thepost-angioplasty surface. A novel method and device for applying aring-shaped tack device as a retaining structure for plaque in the bloodvessel is described in commonly owned U.S. Patent Appln. 11/955,331,filed on Dec. 12, 2007, entitled “Device for Tacking Plaque to BloodVessel Wall”, which is incorporated by reference herein.

Other objects, features, and advantages of the present invention will beexplained in the following detailed description of preferred embodimentswith reference to the accompanying drawings.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 shows a schematic illustration of the invention method forperforation and serration treatment of atherosclerotic plaque.

FIGS. 1A-1C illustrate a preferred embodiment of a delivery device inwhich FIG. 1A shows spikes formed like polymer gum drops on a carrierribbon or strip, FIG. 1B shows attachment of the strips 16 on a balloon,and FIG. 1C shows a compact folded balloon.

FIGS. 2A-2F illustrate another preferred embodiment of the deliverydevice in which FIG. 2A shows the spike in the shape of a sharp pin,FIG. 2B shows how the pin is folded into a mesh, FIG. 2C shows the meshannealed to the outer surface of an expansion balloon, FIG. 2D shows thepin folded into the mesh and under a flap of the balloon, FIG. 2 e showsthe pins deployed when the balloon is expanded, and FIG. 2F shows adetail view of the base of the pin.

FIG. 3 shows the arrays of pins in the above-described embodiment foldedwithin accordion-like flaps along the length of the expansion balloon.

FIGS. 4A and 4B illustrate another embodiment of the delivery device inwhich spikes are deployed from and retracted back into a mechanicalcarrier.

FIGS. 5A-5D illustrate other embodiments of the delivery device whichhas spikes carried or projectable from the surface of a catheter carrierand an external multi-lobed balloon for pressing the spikes incircumferential sections against the plaque.

FIGS. 6A-6C show another embodiment for the delivery device in which thespikes are carried on an accordion-like structure FIGS. 7A-7C show threevariations for mounting a spike on a carrier.

FIG. 8 illustrates an embodiment of the delivery device in which thespikes are carried on a stretchable mesh structure.

FIGS. 9A-9D illustrate various patterns for arrangement of the spikes onthe delivery device.

FIGS. 10A-10C show another embodiment for the spike carrier of thedelivery device in which the spikes are carried on ribbon strips of aslitted metal tube which are biased by shape memory outwardly toward thearterial wall.

FIGS. 11A-11C show a variation of the above-described embodiment inwhich the ribbons of the carrier sheet contain a series of holes.

FIGS. 12A-12C show another variation of the above-described embodimentin which the middle section of the carrier sheet has slitted ribbonswhich are biased outwardly toward the arterial wall.

FIGS. 13A-13C shows a further variation of the spike device in which thespikes are medication-eluting or bearing and left in place afterperforation of the plaque.

DESCRIPTION OF PREFERRED EMBODIMENTS

The conventional practice of compression of plaque by expansion pressureduring balloon angioplasty, i.e., by applying a high pressure expansionforce equally in all directions radially from the inside to aheterogeneous, roughly circumferential plaque structure, can produceunpredictable and inconsistent results. In typical treatment ofatherosclerotic plaques, the angioplasty balloon is inflated with 4 to 8atmospheres of pressure, and pressures up to 22 atmospheres may berequired in some cases. Such high pressures can cause injury to theintima and media in the artery at the treatment location. Arterial wallinjury is one of the major stimulants to intimal hyperplasia, smoothmuscle cell replication and intravascular scarring causing occlusion.Plaque is heterogeneous in nature composed of varying masses of soft andhard materials, calcium and highly variable topography, and can give wayalong paths of least resistance. Therefore, when standard balloonangioplasty is performed, some of the plaque inevitably fractures. Theextent and severity of the fracture, the angiographic result and themorphology of the artery surface that result will vary significantlyfrom one patient to the next. This leads to many cases in which stentsare required to be implanted, which prolongs the surgical procedure, andincreases medical risk and costs. It also leads to exposure of themedial wall of the artery which causes injury. The reparative processfor this injury has been thrombotic and occlusive affects. Moreover, theclinical evidence indicates substantial disadvantages with using stents,including body rejection of a large mass of foreign material, and theemplacement of extensive surface area of a stent that may become sitesfor re-accumulation of plaque and re-stenosis. There is some evidencethat stents may stimulate biological reaction that limits the long-termpatency of the procedure. Stents also cause problems with kinking of theartery in areas where the artery is significantly flexed, such as at theknee joint. Stents may also fracture and break due to material stress.

In the present invention, the plaque is treated by a pre-angioplastypreparation procedure of perforation and serration that form lines orpatterns of microperforations which act as serrations for formingcleavage lines or planes in the plaque. The serrations will result inmore predictable and more uniform expansion characteristics in theplaque during a subsequent balloon angioplasty, thereby helping to makethe balloon angioplasty a more consistent and predictable process. It isexpected that plaque prepared by the perforation and serration procedurecan be dilated with a much lower pressure during angioplasty, i.e., lessthan about 4 atmospheres, and as low as 2 atmospheres or less. Theability to perform angioplasty at lower pressures will create lessplaque dissection and less arterial injury. Less arterial injury maylead to better rates of acute success because there is less dissection,and may also lead to better long-term results since there is less injuryto the intima and media in the artery at the treatment location.

The forming of serrations in the plaque through microperforation isdeemed to provide a line along which expansion energy may be released.The microperforations are formed in a pre-angioplasty procedure ofinserting a carrier carrying an array of small, sharp spikes which arepressed under a slight expansion force to pierce partway into the plaqueand without causing injury to the arterial walls. Since plaque usuallyfractures longitudinally during standard balloon angioplasty, the spikesare preferably arranged in a mostly longitudinal pattern. Othervariations include configurations with a diagonal or zig-zag patternconsistent with the expected ways that plaque commonly fractures. Theheight of the spikes is designed to pierce the plaque surface to createserrations for expansion lines, but not deep enough to cut though theplaque thickness. Materials research on crack propagation can be appliedto select the optimal configurations for spike patterning to obtain thebest characteristics in plaque compression.

Artery vessels are comprised of organized lamellar structure withrepeating structural and functional units of elastin, collagen andsmooth muscle cells. The lamellar structure is prone to split and createa cleavage between adjacent elastic lamellae. Basically, in angioplastythe expansion is partly due to the arterial stretching. In addition theplaque material has low ductility and fracture stresses can propagatenon-uniform cracks in the brittle material. In the pre-angioplastypreparation of the plaque material, the microperforations act asnucleation sites for void formation. In the subsequent application ofballoon angioplasty, stress energy for compressing the plaque isreleased along the serration created by the series of pinpoint voidsformed in the plaque to control crack propagation. If balloonangioplasty is applied without the plaque serration step, the amount ofstress energy applied can be very high prior to initiation of crackformation, and once the crack begins the energy can quickly propagatealong brittle crack areas, leading to unpredictable plaque ripping,tearing, or dissecting. The plaque does not give way until the forceapplied by the balloon has overwhelmed the plaque. At that point, thecrack or dissection is rapidly propagated along the plaque, thusworsening the dissection. The pre-angioplasty preparation of the plaquewith microperforations avoids high stress concentration at an initialpoint of fracture, and assists stress release along the series of voidsdesigned to guide the fissure event and provide more predictablecleavage lines in the plaque.

The perforation and serration procedure will promote more uniformcompression of the plaque under expansion pressure during angioplasty.The portion of the plaque that does not compress will expand better andwill be less likely to break or fracture. Forming serrations in thesurface of the plaque is expected to provide better and more uniformcompression under low pressures in angioplasty and will produce betterplaque compression characteristics than the standard approach ofapplying high expansion pressures against the full length, width, andthickness of the plaque. This is expected to result in compressing theplaque with fewer tendencies for dissection, allowing the plaque to openalong more natural lines, and therefore expanding the lumen larger andwithout causing arterial injury.

The perforation and serration procedure is expected to providesignificant advantages as compared to prior proposals for cutting orscoring the plaque with blades or sharp edges during the balloonangioplasty procedure. Some prior proposals have called for performingballoon angioplasty with longitudinal cutting blades affixed to thesides of the angioplasty balloon. However, in order to push the cuttingor scoring blades into the plaque, high forces are required. Moreover,at the typical high pressures for balloon angioplasty, the cuttingblades or scoring blades forced into the arterial walls experience evenhigher pressures at the blade interface surface, because all the forceof the balloon is concentrated on the projecting cutting blades orscoring wires. This high pressure angioplasty creates unnecessaryinjury. Because the cutting or scoring action of the blade is performedat the same time as the expansion of the artery with balloonangioplasty, there is no prior preparation of the plaque before balloonangioplasty and there is a risk that the artery itself may be cut andforced open as the pressure is released during the fracturing event. Theartery may thus be injured in a traumatic manner and at high pressures.The deeper layers of the artery, such as the medial layer or deeper maybe exposed or cut or scored or otherwise injured by this device, withthe pursuant sequella of artery wall injury. Cutting blades, or scoringwires or edges also have relatively long linear lengths that will cutacross non-uniform plaque material, producing uneven cuts and unevenpressure distributions. Even smaller cutting blades will encounter attimes areas of dense calcification among softer masses that could befractured by the linear cutting blades or edges. The longitudinallyoriented cutting blades or scoring wires may also be placed acrossnormal or less diseased artery wall surface. Cutting or scoring of theseareas can not skip areas where there is little or no plaque, creatingeven more injury. In contrast, microperforations form tiny holes atspecific prick points across the plaque mass and taken together as aline or pattern of perforations result in more reliable serrations. Ifthe barbs that create the microperforations encounter normal or lessdiseased artery surface, there is less likelihood of injury due in partto the shallow depth of penetration since the expansion of the Spikedevice is intended not to perform simultaneous full diameter angioplastybut to prepare the plaque and is therefore expanded to a much lesserdiameter than intended for the final result for the artery. In addition,if a barb did happen to go into the wall of the artery at a locationthat is not needed for treatment (that is, plaque preparation), theresult would be a punctuate microperoration, not a crater, canyon orcrevice, as is routinely created by scoring or cutting devices.

Other prior proposals have suggested scoring the plaque with a metalwire or tabs arranged around an angioplasty balloon in a spiral ordouble spiral manner. The outer wire or tabs may be forced into the wallof the artery when the balloon is expanded during angioplasty at highpressure. The orientation of the wire on the outside of the angioplastyballoon focuses the expanding balloon pressure on the wire. Thereforethe pressure exerted by the wire against the wall of the artery farexceeds the pressure in the balloon generating a very high localizedpressure at the working tip of the wire. The wire or tabs may cut deeplyinto the wall and may cause increased injury beyond that caused by thehigh pressure alone. In addition, because the wire is wrapped around theballoon in a spiral manner, the distance between the wire windingsaround the outside of the balloon will change at different balloondiameters. This causes some axial displacement of the wires so that itmay actually undermine artery plaque by causing it to “dig up” theplaque. This may even create dissection planes that are morecircumferentially oriented (as opposed to longitudinal) and may be morelikely to function as flow limiting dissections.

In contrast, the perforation and serration procedure can be performed atlow balloon or other expansion pressures. The microperforations areformed by small sharp spikes which can pierce into the plaque withoutdigging it up. Forming tiny prick points with the small spikes willleave most of the surface of the plaque intact, will not injure thearterial wall, and will leave most of the plaque structure intact formore predictable and better compression characteristics. The serrationsallow the plaque to be compressed at lower pressures during thefollowing angioplasty. The plaque is also less likely to formdissections, both because it can be treated at lower pressures, andbecause the plaque has expansion lines serrated in it that allow it toexpand in a more orderly manner.

Because the perforation and serration procedure forms small prick pointsin the plaque, it may also afford a very effective means of distributinganti-plaque medication or other biologically active medication or stemcell delivery into the plaque from a drug-eluting balloon duringangioplasty or from a drug-eluting stent after angioplasty. Themicroperforations may serve to retain more medication within the plaquemass, acting as a portal to the inner structure of the plaque for themedication to work. In the pre-angioplasty procedure, the spikes mayalso be used as a carrier for drug delivery by coating the spikesthemselves with drugs.

The perforation and serration procedure is thus designed as a minimallyinvasive approach for creating predictable cleavage planes inatherosclerotic plaque in preparation for balloon angioplasty. Thecleavage planes are enabled by the serrations formed by numerous smallperforations into the plaque in a predetermined pattern on the plaquesurface. By creating a preformed expansion line or line of cleavageprior to angioplasty, the artery is prepared so that it will respond toballoon dilatation in a more predictable manner with less likelihood ofdissection or elevated surface flaps. The need for stent placement tosmooth the artery surface and retain plaque dissections or flaps canthus be significantly decreased.

A suitable device for performing the perforation and serration proceduremay be designed in a number of ways, as described below for thefollowing preferred embodiments which are illustrative of the principlesof the present invention. Three different methods for spike deployment,through mechanical, balloon, and balloon-assist deployment, aredescribed with respect to certain preferred delivery designs. Thelocations, length, and configuration of the spikes may be designed forvarying types of lesions and arterial sites being treated. For example,heavily calcified lesions may require that the spikes be more closelyspaced and penetrate a little deeper into the plaque. Some devicedesigns may only be partially covered with spikes so that the hardestpart of the plaque is left alone and serrations are created along asofter portion of the plaque surface. Lesions that are morelongitudinally oriented may require spike placements that are fartherapart and arranged in a gradual twirling configuration.

FIG. 1 shows a schematic illustration of the invention method forperforation and serration treatment of plaque 10 at a site in an artery11 with a delivery device 12 for serration and dilatation of the plaque.The lumen L is the flow opening in the artery that has been occluded byplaque 10. The device 12 has one or more arrays 12 a, 12 b, and 12 c ofsmall, sharp spikes carried on carrier strips or surfaces which areseated on the outer surface of an expansion balloon 14 or otherexpansion device. The spikes are mounted on the carrier strips at spacedintervals and extend typically a distance 0.05 mm to 1.0 mm beyond thecarrier surface for piercing into the plaque and formingmicroperforations across the surface of the plaque. The delivery device12 may be carried in a catheter and positioned at the plaque site byinsertion into the artery through a surgical incision (not shown) andmanipulated into position by a wire 13 to the location of the plaque.The spikes and expansion balloon are initially in a deflated orcollapsed state to allow threading of the device 12 through the artery.

When the delivery device is in position, and a catheter shield (if used)is retracted, the expansion balloon is inflated through an inlet tube 13at low gas or fluid pressures to gently push the spike arrays againstthe plaque 10. Gas or fluid pressures of about 4 atm or less may be usedfor the pre-angioplasty procedure, and preferably a very low pressure of2 atmospheres or as low as 1 atmosphere is used. The spikes createseries of microperforations which act as serrations along the horizontallength of the plaque. The serrations allow cleavage lines or planes tobe formed in the plaque at these locations under compression forcesduring a following angioplasty procedure. As the spikes are pressed intothe plaque, the plaque is also compressed gently for a given measure ofdilatation. When the serration has been performed, the balloon isdeflated by suction of fluid or gas out through the tube, such that thedelivery device 12 can resume its collapsed state so that it can bewithdrawn from the artery.

A standard angioplasty balloon may thereafter be used to compress theplaque against the artery walls to open the lumen. The compression ofthe plaque during angioplasty can take place evenly and with minimaldissection or cracking along the cleavage lines formed by themicroperforations. Due to the pre-angioplasty preparation of the plaque,the balloon angioplasty can be performed at low pressures of less than 4atmospheres, and as low as 2 atmospheres of pressure or less. If thepre-angioplasty procedure has compressed the plaque sufficiently, it maynot be necessary to follow it with a standard angioplasty.

FIG. 1A illustrates a preferred embodiment of the delivery device inwhich the spikes are formed like polymer gum drops 15 on a narrow ribbon16. The polymer is heated and fed in liquid form to an ejector thatejects a drop in position on the ribbon. The drop rapidly cools as it isejected, and forms an inverted cone shape that comes to a hard sharppoint by tapering off the fluid from the ejector. The potential shape ofthe spike can include other types of pointed shapes, such as a long,pyramidal shape, a triangle shape, an arrow shape (longer and sharp inone axis and narrow and dull in the perpendicular axis), a gum dropshape, a narrow rectangle shape, a pin shape, a needle shape, andothers. Other materials could be used to form the spike, including apliable metal, such as Nitinol, or carbon nanotubes.

After hardening and processing of the polymer, the narrow strip 16 isannealed to the surface of an expansion balloon or other mechanicallyexpansive carrier. The strips may also be interwoven into a mesh(polymer, metallic, or fabric). The strips or mesh are arranged in apattern that envelopes the surface of the expansion balloon or othermechanically expansive structure. FIG. 1B shows attachment of the strips16 (end view) along the longitudinal length of a balloon 17 at a number(8) of circumferential positions. The balloon may be folded at folds 18to bring the sharp points 15 on four adjacent strips to nest with thoseof the other strip, and then the two lobes of the balloon are foldedover again to bring the sharp points of the other four adjacent stripsinto nested configuration. FIG. 1C illustrates the resulting, compactfolded balloon in which all the sharp points are folded within to avoidengaging the plaque material when the device is being moved intoposition.

FIG. 2A illustrates another preferred embodiment in which the spike isin the shape of a sharp pin 21 that has a lower end bonded to a mesh 22that is annealed to the surface of the expansion balloon. The lower endof the pin 21 is held by the polymer mesh so that the spike stands erecton the surface of the balloon when the balloon is inflated. The pin 21may be constructed of polymer, metal composite, silicon or carboncomposite or carbon nanotubes (single or multi wall).

FIG. 2B illustrates how the pin 21 is folded by pressing it into themesh 22. In FIG. 2C, the mesh 22 is shown annealed to the outer surfaceof the expansion balloon 23. In FIG. 2D, the pin 21 is laid downlaterally and perpendicularly to the axis of the balloon center line forplacement, so that the pin is folded into the mesh and under a flap ofthe balloon. The entire mesh in the depressed mode is nearly swallowedup by the balloon material. With the pin laid down flat within the mesh,the balloon is protected from puncture of the balloon surface. The flapon the balloon unfolds during balloon expansion, and the meshes areunfolded so that the pins are quickly popped out straight and erect.

FIG. 2E shows the pins 21 deployed and standing erect on the expansionballoon 23 after the catheter shield 24 is withdrawn and the balloon isinflated. The pins are exposed and stand erect on the mesh sheets 22that are mounted on the balloon surface. The pins stick out peripherallyand can pierce into the plaque as the balloon is further inflated. FIG.2F shows a detail of the base of the pin 21 entwined in the mesh weavingto center the lower end of the pin on the mesh 22 and hold the pin erectwhen the mesh is unfolded and the balloon is expanded.

In FIG. 3, arrays of pins 21 are shown folded within accordion-likeflaps of a pre-angioplasty expansion balloon 23 of the device which arefolded in alignment with a longitudinal axis LG of the balloon. In thisdesign, half the flaps and pins are folded toward one end of theballoon, and the other half are folded toward the other end of theballoon. When the balloon is expanded, the mesh strips will reorientwith respect to the surface of the balloon and face outward toward theplaque on the artery walls. The flaps of balloon material betweenparallel rows of spikes can be made extra flexible and pliable and maybe formed as a folding crease. When gas or fluid pressure is injected inthe balloon, the flaps are the first areas to pop out and help to pointthe spikes outwardly toward the plaque.

FIGS. 4A and 4B illustrate another embodiment of the delivery device inwhich an expansion balloon is not used but rather the spikes 41 aredeployed from and retracted back into a mechanical carrier 40. Thecarrier has a plurality of tunnels 42 a in its interior each of whichholds a spike in a ready position within and has a spike exit hole 42 bwith its axis oriented radially to the outer surface of the carrier.When the carrier 40 is in position at a plaque site, the spikes aremechanically or hydraulically actuated, such as by an gas or fluidpressure force indicated by arrows 43, to travel through the tunnels andproject radially from the spike exit holes 42 b. The spikes have sharppoints at their tips for creating microperforations in the plaque, butare flexible in their shafts so that they can be deployed from a layingdown position and turned to a 90 degree standing up position. In thatposition, the spikes are pointed toward the wall of the artery and theplaque. As an alternative for mechanical actuation, the spikes may beactuated by respective levers which are pulled or pushed by a cable.Other types of mechanisms similarly may be used for mechanicallydeploying the spikes from the carrier. This embodiment may also be usedto shoot or impregnate the plaque surface with spike devices that aredesigned to be left in the plaque.

FIGS. 5A-5D illustrate other embodiments of the delivery device forpre-angioplasty serration and dilatation. In the embodiment shown inFIG. 5A, rows of spikes 51 are bonded to a ribbon, rod, triangle orother shaped carrier 50. An outer balloon 52 is divided into quadrantsand shaped with cutout areas that conform to spaces in between thespikes. The balloon 52 is inflatable in quadrants circumferentiallyaround the carrier 50. As one quadrant of the balloon 52 is inflated,the spikes on the opposing side of the carrier 50 are pressed into theplaque on the artery wall. The balloon 52 on the side of the onequadrant is deflated, then the next quadrant is inflated to press thespikes on another opposing side into a next section of the plaque. Thisis repeated for the other quadrants as needed until the spikes on allsides have been pricked into the circumference of the plaque surface.

In FIG. 5B, another embodiment of the delivery device has rows orribbons of spikes 53 bonded to an internal carrier balloon 54 sleevedinside of a tube 55 which has spike holes 55 a aligned with thepositions of the spikes spacing found on the internal carrier balloon54. An outer balloon 56 is shaped with cutout areas that conform to thespaces between the spike holes. The outer balloon is able to be filledin quadrants circumferentially around the carrier device. As onequadrant expands, the tube is pressed on its opposing side against theplaque. The internal carrier balloon 54 is inflated and the spikes arepressed out of the holes and pierce into the plaque on the side incontact with the plaque. This is repeated for the remaining quadrantsuntil the spikes have been pricked into the circumference of the plaquesurface.

In the above-described embodiments, the multi-lobed segments of theexpanding balloon stabilize and support the spikes as they enter theplaque to cause perforation. The spikes may be constructed of anysuitable material, such as polymer, pliable metal, or carbon nanotubes,and may have one of many possible shapes, including a pin shape, aneedle shape, a long, pyramidal shape, a triangle shape, an arrow shape,a gum drop shape, a narrow rectangle shape, and others. The balloon, asit is expanded, is also used to compress the plaque to a certain degreeand dilate the lumen of the artery. The balloon may be manufactured tobe inflated with CO2 or with liquid.

FIG. 5C shows another embodiment where rows of spikes 57 are bonded toor etched out of a ribbon, rod, triangle or other shaped carrier 58. Anouter balloon 59 is multi-lobed capable of being inflated in sectionsand conforming to spaces in between the spikes. FIG. 5D shows a furtherembodiment in which the spikes 57 are seated on an inner balloon in adelivery catheter 58. The catheter walls have holes 58 a located toallow the spikes to poke through when the inner balloon is inflated. Onthe outside of the catheter in this embodiment is multi-lobed externalballoon 59 which is inflatable in sections. As one section is inflated,the catheter wall on the opposite side is pushed against the plaque onthe arterial wall, and when the inner balloon is inflated, the spikes 57are pressed out to pierce into the plaque mass. This procedure isrepeated in sections circumferentially around the catheter until allareas of the plaque have been pierced by the spikes.

FIGS. 6A-6C show another embodiment for the delivery device in which thespikes (welded, bonded, or shaped out-of-plane) are carried at joints onthe circumference of an accordion-like structure provide for amechanical expansion engagement with the plaque. In the pre-loadeddelivery position shown in FIG. 6A, the accordion-like structure 60 isstretched longitudinally over the surface of the delivery catheter 61,and the spikes 62 lay flat against the catheter sheath. This position ofthe spike structure is used when the catheter is inserted and withdrawn.Once the spike structure is in position at the plaque site, theaccordion-like structure 60 has its opposite ends moved together, suchthat the spikes 62 are pressed out radially to pierce the plaque, asshown in FIG. 6B. The compression of the accordion-like structure 60 maybe actuated by mechanical pulley, polymer fiber or wire attached atpoints A disposed symmetrically around the circumference of thecatheter. The wires are pulled uniformly at one end of theaccordion-like structure to compress lattice segments of the structureand decrease the distance between the spike connector joints, therebyforcing the spikes outwardly toward the lumen wall. In FIG. 6C, theaccordion-like structure is shown laid out in plan view and elevationview, and pre-loaded in end view.

FIG. 7A-7C show three variations for mounting a spike on a carrier. InFIG. 7A, the spike 70 (pyramid point) is mounted on a button 71 havinglower shanks 71 a for seating on a carrier. In FIG. 7B, the spike 72(pin) is mounted on a button 73 having button holes 73 a for attachmentby fasteners to the carrier. In FIG. 7C, the spikes 74 (sharp tips) aremounted on a button 75 having holes 75 a for fastening to the carrier.The buttons may be entwined within a fabric, woven pattern or bagstructure using the button holes or mounting shanks on the buttons.These spike-mounting buttons may be used with any of the above-describedembodiments for the delivery device.

FIG. 8 shows an embodiment in which the spikes are carried on astretchable mesh structure 80 surrounding an expansion balloon which isinflated to stretch the mesh outwardly on all sides and push the spikesinto the surrounding plaque mass. The spikes may be interwoven into themesh structure. When the balloon is deflated, the mesh snaps back withthe collapsed surface of the expansion balloon. Another variation forthis embodiment is the use of the balloon-restricting mesh which, whenplaced over the expansion balloon, the mesh restricts the balloonsmaximum expansion diameter so that it is less than the blood vesseldiameter. The mesh minimizes the potential of the balloon to expandbeyond the stenosis site into an hour-glass shape, which is a commonproblem when the balloon length is longer than the stenosis length. Ifthe balloon spans beyond the plaque on both sides, the inflationpressure in the balloon tends to fill the areas of least resistancefirst, so it fills on opposite sides of the plaque first. As the balloonpressure increases, the pressure on the healthy vessel walls on theopposite sides becomes equal to or greater than on the diseased portion.The balloon-restricting mesh limits the hour-glass effect and provides amethod to control the applied pressure to the region where the lumenneeds the expansion. The mesh also limits the amount of pressure that isdelivered to the plaque by limiting it to a defined radial expansion.The mesh may be shaped like a “Chinese finger trap” that is restrictedin its ability to open, and may be made of nitinol, stainless steelwire, polyethelene filaments, or other inert material.

The balloon restricting mesh prevents bulging of the balloon and evensout the pressure of the balloon on the wall of the artery and preventstoo much force from the balloon in any one place and thus limitsdissection and damage. In addition, the mesh itself may change thetopography of the plaque surface in the same way that microperforationsdo, i.e., creating many small indentations in the plaque surface so thatthe plaque can relax evenly when it is dilated.

In all the embodiments described above, the spikes may be made frommetal, polymer, silicon or carbon composite (with or without an inertcoating), a super-elastic material, or carbon nanotubes. The spikes mayhave a preferred height (from base to tip) of 0.05 mm to 1.0 mm. Thespike tip may be needle-like with a needle head for mounting. As analternative, the tip can be shaped with a thin tubular cross-section (asin a needle for transporting fluid through it), or a groove or slothaving one dimension that is much larger than the other where the largerdimension of the groove is less than 2 mm and the smaller dimension ismuch less than the first, and a point where the overall head radius issmall less than 0.4 mm (as in a pin head), or a collection of very smallpoints where the overall head radius is less than 0.05 mm (as in carbonnanotubes). It may instead be formed by carbon nanotubes presenting acollection of very small points to form a sharp tip. The spikes may alsobe coated with, or provide transport for, plaque-inhibiting medicationfor deposition into the plaque site. In the preferred embodimentsdescribed above, the spikes may be mounted on the surface of a balloon,or on a catheter, or may be mounted on a mechanically actuated surface.The spikes may have various shapes, may be made from a variety ofmaterials, may be deployed in different ways, and may be attached to thedelivery device using different methods. The spikes are arrayed in anydesired pattern to create a cut-along-the-dotted-line serration in theplaque mass so that it can become a cleavage plane or expansion planeduring dilatation by balloon angioplasty. The configuration of thespikes may be oriented in different manners depending upon the arterialdisease and the plaque formation requiring treatment. The spikes mayalso have through-holes or inner channels for eluting medication throughthe spike to the surface of the plaque. The spikes may also beprotruding components of the balloon restricting mesh.

FIGS. 9A-9D illustrate various patterns for arrangement of the spikes onthe delivery device, i.e., circumferential, partial circumferential,patch, spiral/diagonal, and longitudinal. The configurations aredesigned for different functional purposes in managing atheroscleroticplaque or in ease of manufacture or ease of use. Plaque with certaincharacteristics, such as very heavy calcification, may be treated withspikes that are configured in more of a circumferential or diagonalpattern, crossing the line of blood flow, since this morphology ofplaque tends to form clusters or mounds of calcium. The spikes that maynot be able to perforate this type of plaque or portions of this type ofplaque very readily, but may be able to cut around the areas of worsedisease and permit the inner circumference of the whole artery toexpand. The spikes are arranged generally longitudinally, consistentwith the fracture characteristics of plaque in most situations and withmost plaque morphologies, and may be configured in a straight line. Thestraight, longitudinal lines of spikes may be very short, consisting offive spikes or less and may be quite long, consisting of 100 spikes ormore. The longitudinal lines of spikes may be very close together, withas many as 20 lines distributed on the circumference of the arteryluminal surface, or there may be as few as a single line of barbs orspikes. The lines of spikes may also be in a slight diagonal or in azig-zag fashion. The configuration of the barbs or spikes is determinedin accordance with the best expected mechanism for post-angioplastyplaque dissection. They are designed to create cleavage planes orexpansion lines suitable for the expected composition of the plaque andthe pressures expected to be exerted upon it. The orientation and depthof desired cleavage planes may vary significantly with the parametersfor balloon angioplasty. The spikes may also be constructed so that theymay provide delivery of medications. A cooperative structure such as adouble-walled balloon for pressure infusion of a small amount ofmedication agent into the plaque wall or other functionality may also beincluded.

FIGS. 10A-10C show another embodiment for the spike carrier of thedelivery device. In FIG. 10A, the spikes are carried on ribbon strips ofa slitted metal sheet which has opposite ends that are joined by eitherwelding into a tube or the strips are cut out of a tube leaving one endintact. The spikes may have various profiles, such as where the lengthof the spike base or head is equal to the width of the ribbon strip, orthe spike base is a fraction of the ribbon width and is centered at themiddle of the ribbon strip, or where the spike base is a fraction of theribbon width and positioned at varying locations across the ribbon widthor may have multiple spikes at any given ribbon section of width. FIG.10B is an elevation view of the sheet. FIG. 10C shows the sheet afterheat treatment to provide a shape memory in which the ribbons arespring-biased radially outward toward the arterial wall for generatingperforations in the plaque. The shape memory may be used alone formechanical engagement of the spikes, or may be combined with anexpansion balloon to allow greater control of forces to be applied.

FIGS. 11A-11C show a variation of the above-described embodiment inwhich the ribbons of the carrier sheet contain a series of holes. Theholes serve as points for attachment of strings, cables, or wireelements, configured in such a way, that when pulled can provideadditional support and force outward against the lumen wall. FIG. 11B isan elevation view of the sheet. FIG. 11C shows the sheet after heattreatment to provide a shape memory for spring-biasing the ribbonsradially outward. The shape memory may be combined with an expansionballoon to allow greater control of forces to be applied.

FIGS. 12A-12C show another variation of the above-described embodimentin which both longitudinal ends of the tube are kept intact, leavingonly the middle region with slitted ribbons. One end contains a seriesof holes which serve as points for attachment of strings or wireelements that when pulled can provide additional support and forceoutward against the lumen wall. FIG. 12B is an elevation view of thesheet. FIG. 12C shows the sheet after heat treatment to provide a shapememory for spring-biasing the middle section of ribbons radiallyoutward.

A general procedure for the pre-angioplasty perforation and serration ofa plaque site will now be described. A delivery catheter is constructedfor the purpose of plaque perforation in an endovascular environment. Aguidewire is threaded along an artery from a percutaneous access site ora surgical incision to a lesion intended for treatment. A catheter ispassed over the guidewire with an end of its sheath maintained gas-tightand fluid-tight for operational control externally by an operator. Aspike delivery device is advanced down the hollow, tubular shaft of thesheath over the guidewire and the spike delivery catheter is inserted inposition at the lesion. The delivery device for the typicalperforation-serration catheter is intended to be as large as 8 Fr andmore likely 5 Fr or less in diameter. The guidewire lumen maybe 0.014inch or up to 0.035 inch in diameter. The length of the deliverycatheter may be as short as 30 cm but more likely 75 to 80 cm for ashort length and 120 to 135 cm for a long length. The catheter hasanother tubular channel for inflating or actuating the expansion balloonor other actuating apparatus on the delivery end of the catheter.

When the expansion balloon, mechanical expansion apparatus or otherapparatus is actuated, the spikes on the delivery device are pressedtoward the plaque. The spikes are driven into the plaque and createmultiple perforations forming intended serrations in the surface of theplaque in a proscribed pattern. The expansion balloon or apparatus issomewhat compliant and may be inflated further to compress the plaqueand enlarge further. However, the device is typically not intended toenlarge the plaque to as large a diameter so as to restore its lumenback to normal and fully intended size. When the desired perforation ofthe plaque has been achieved, the expansion balloon or apparatus isde-actuated, disengaging the spikes from the plaque, and once collapsedis withdrawn through the catheter sheath.

After the preparation procedure for the plaque, the plaque can becompressed and the artery lumen safely and accurately dilated andstretched during standard balloon angioplasty to its intended diameterwithout creating numerous and substantial dissections and elevatedflaps. The perforation and serration enable the plaque to be dilatedmore evenly and smoothly and avoid forming random cracks that may leadto dissection, arterial injury, and residual stenosis. The plaque, afterit has been pre-treated with perforation and serration, may also bedilated with lower pressure (usually 2 atmospheres or less) than thatwhich is used in standard balloon angioplasty. The lower intra-balloonpressure causes less injury to the artery wall. This “low pressure” or“minimal injury” angioplasty is less likely to cause the biologicalreaction that often follows balloon angioplasty with neointimalhyperplasia or smooth muscle cell replication. There is less likelihoodof exposing or damaging the medial layer of the artery. In addition, theplaque is likely to expand with less fracturing or dissection duringballoon angioplasty. This decreases the need for stent placement to beused to treat dissection or residual stenosis after balloon angioplasty.If extensive dissections and non-smooth luminal wall surfaces require astent to be placed, the improved dilatation of the lumen obtained withpre-angioplasty perforation and serration would allow a stent to be morefully opened.

While there have been prior proposals for providing blades or sharpedges or scoring wire on a balloon during angioplasty for cutting orscoring the plaque in conjunction with balloon expansion, these priormethods are deemed to have problems or disadvantages which areeliminated or avoided by the pre-angioplasty treatment in the presentinvention. Cutting or scoring the plaque during angioplasty is performedat high pressures that can result in high injury to the blood vessel.The cutting blades, edges or scoring wire are forced into the wall ofthe blood vessel at the same time that the angioplasty balloon isexpanded to dilate the plaque. During this process the cutting blades,edges, or scoring wire can be forced into the vessel wall at obliqueangles and can plow up the plaque potentially increasing the tendencyfor dissections. In contrast, the pre-angioplasty treatment in thepresent invention employs spike elements that are expanded into theplaque at low pressures so as to form precise microperforations in aradially outward direction that form precise cleavage lines or planes inthe plaque. The spikes project sharp points that push into the plaque insmall surface areas, thereby being much less likely to plow up theplaque.

For the described embodiments of the spiked device, the depth of themicroperforations can be in a range of 0.01 mm to 0.5 mm. The distancebetween perforations can range from 0.01 mm to 2 mm, and typically maybe equal to or greater than the depth of the spikes. The ratio ofmicroperforation spacing to depth preferably is about 1:1 or more. Thespikes may also be formed with a serrated edge or a syringe-like pointthat has one pointed side longer than its opposite side. Another spikehead variation can have multiple pointed tips at varying heights. Thesevariations can provide the ability of the spike tip to be perforate intorigid plaque more effectively.

The pre-angioplasty treatment of a plaque site may also be combinedinstead with drug-eluting balloon (DEB) angioplasty or drug-coatedballoon (DCB) angioplasty. In DEB or DCB angioplasty, medication istransferred to the plaque and/or wall of the blood vessel duringexpansion of the angioplasty balloon at the site of the angioplastytreatment. Due to the various applications of balloon angioplasty, thereare a variety of medications that may be used, such as plaque-reducingmedication, medications that inhibit tissue in growth, delivery of stemcells and others. The intended effect is to have the medication taken upby or adhered to the plaque and/or wall of the diseased artery at thetime of balloon angioplasty. The method of coating the balloon may varyand may include simple placement of the balloon into the medication fora period of time or using an agent that binds the medication temporarilyto the balloon. Independent of the coating used, the balloon angioplastymechanism used in DEB has not been changed significantly from originalballoon angioplasty. The balloon is cylindrical in shape and is placedat the site of plaque accumulation and is pressurized. When the pressureaccumulates within the balloon, it exerts a force upon the plaque andembeds or coats the plaque with the medication.

If standard DEB angioplasty is used without the plaque-preparation step,the amount of initial surface contact is defined by the morphology ofthe lumen. The pre-DEB angioplasty preparation of the plaque withmicroperforations will provide a less rigid and constrained surface.

The ability of the atherosclerotic surface to retain a more openstructure, accessible to the DEB surface as it expands, is achieved bypre-angioplasty serration. The result is plaque relaxation, opening upnumerous microfissure planes, allowing the plaque surface to generate amore uniform intraluminal surface roughness while minimizing the typicaltearing associated with angioplasty that generates unpredictableintraluminal surface roughness. The creation of microperforations in thesurface of the plaque provides more plaque surface for treatment withthe medication that is introduced during the DEB angioplasty. Inaddition, because the perforations are in the surface of the plaque, themedication will be placed specifically where it will have some effect onthe plaque. By adding microperforations, the drug-contacting area isincreased, permitting better adherence and uptake of medication.

The following chart summarizes a comparison of impacts and cost factorsfor traditional angioplasty, DEB angioplasty, and DEB angioplasty withspike preparation:

Factors for Traditional DEB Spike prepped Comparison AngioplastyAngioplasty Angioplasty Injury/Plaque Disruption Severe Severe MinimalPressure on Artery Severe Severe Minimal Stimulates Growth of ModerateAnticipated Minimal Re-stenosis minimal Cost Higher-more Higher-moreLower-less need need for need for for stents stents stents

As another variation, the spike device can have drug-coated tips, or aninternal drug-containing reservoir where each spike behaves like asyringe. A bladder on the outer surface of the spike can be pressedunder the expansion pressure of the spike-delivery balloon and injectedinto the plaque through a capillary in the spike body or along itssurface.

FIGS. 13A-13C illustrate a further variation of the spike device inwhich the spikes are medication-eluting or bearing and left in placeafter perforation of the plaque. Upon penetration of the spikes into theplaque wall in FIG. 13A, the spikes on the device surface are driveninto the wall (through expansion pressure of the balloon) and are leftbehind as the device retracts, as shown in FIG. 13B. The spike headsthat are left behind (like the spines of a porcupine) may offer thefollowing unique functions: (i) capable of injection of medication, STEMcells, or other agents designed to facilitate arterial health; (ii)infused with medication in the spine head surface or through the spinebody matrix; (iii) medication contained within a vial in the center ofthe spines; and/or (iv) fabricated of bio-degrading or bio-absorbablematerial. If the spikes are made of bio-degrading or bio-absorbablematerial, over time the spikes are degraded or absorbed and leave behindonly the perforation holes, as shown in FIG. 13C. Due to the greaterpenetration and surface area contacted, the left behind spikes wouldprovide greater infusion of medication into the diseased area. Avariation includes spikes where the base is pre-biased to expandlaterally capturing surrounding plaque tissue and tacking it to thelumen wall.

As an alternative to stent emplacement following balloon angioplasty, incases where one or more local sites of post-angioplasty dissections orflaps present themselves, a thin, ring-shaped tack device may be placedat only the location of each specific problem site, so that the amountof foreign material emplaced as a retaining structure for plaque in theblood vessel can be minimized and exert only low lateral pressuresagainst the post-angioplasty surface. A novel method and device forapplying a ring-shaped tack device as a retaining structure for plaquein the blood vessel is described in commonly owned U.S. Patent Appln.11/955,331, filed on Dec. 12, 2007, entitled “Device for Tacking Plaqueto Blood Vessel Wall”, which is incorporated by reference herein. Thedescribed procedure for perforation and serration of the plaqueperformed with a given amount of arterial dilatation may be sufficientto obtain compression of the plaque sufficiently that no balloonangioplasty or stent emplacement is required. Only one or a few of thering-shaped tacks may be needed to secure the compressed plaque to theartery wall, thereby obtaining the desired medical treatment withminimal forces being applied to the arterial walls and with a minimum offoreign material emplaced in the body. The present invention istherefore deemed to include the alternative of combining the perforationand serration procedure with the procedure for applying localized tacksat specific locations for plaque retention.

Many related benefits, advantageous variations and more functionalextensions may be developed or adapted from the above-describedprinciples of the invention, such as the following. In thepre-angioplasty perforation procedure, the spikes may actually be partof a balloon restricting mesh limiting the balloon expansion size, sothat if the spikes are placed into segments of the artery with lessdisease, they do not go into the artery wall because the diameter ofexpansion of the spikes is kept smaller than the artery size. Thepre-angioplasty perforation procedure enables medication from thesubsequent DEB angioplasty to be taken up by the artery in greateramounts and with more efficiency. Microperforations may be arranged witha size, patterning, and strategic positioning relative to the plaquesurface that not only optimizes plaque relaxation and expansion butfacilitates uptake and activity of medication (including stem cells).The balloon angioplasty performed after perforation preparation is lesslikely to expose the medial layer of the artery wall, less likely tocause injury. The spikes may be specifically designed for the rightsize, shape configuration, etc to be optimal for different kinds ofplaque. The microperforations can be arranged to create spaces in theoptimal places in the plaque for medicine from the DEB to bebiologically active. The perforation procedure may also be applied toother tubular structures in the body such as uritor, billiard tree, venacava, intestines, peripheral veins, Schlemm's canal, and the like.

It is to be understood that many modifications and variations may bedevised given the above described principles of the invention. It isintended that all such modifications and variations be considered aswithin the spirit and scope of this invention, as defined in thefollowing claims.

1. An intravascular device for perforation and serration ofatherosclerotic plaque prior to balloon angioplasty, comprising acarrier carrying lines or patterns of small sharp spikes, and anexpansion apparatus for pressing the spikes to pierce a luminal surfaceof the plaque with lines or patterns of microperforations which act asserrations for forming cleavage lines or planes in the plaque.
 2. Anintravascular device according to claim 1, wherein the spikes andcarrier are drug-coated.
 3. An intravascular device according to claim1, wherein the spikes each have an internal drug-containing reservoir sothat it behaves like a syringe.
 4. An intravascular device according toclaim 1, wherein the spikes are detachable from the carrier and aremedication-eluting or bearing so that they are detached and left inplace after perforation of the plaque.
 5. An intravascular deviceaccording to claim 4, wherein the spikes are made of bio-degrading orbio-absorbable material, so that over time the left-behind spikes aredegraded or absorbed and leave behind only the perforation holes.
 6. Anintravascular device according to claim 1, wherein the expansionapparatus is an expansion balloon.
 7. An intravascular device accordingto claim 6, wherein a balloon-restricting mesh is provided over theexpansion balloon for restricting its maximum expansion diameter so thatit is equal to or less than the blood vessel diameter.
 8. Anintravascular device according to claim 6, wherein a balloon-restrictingmesh is provided over the expansion balloon for restricting a tendencyto balloon out at its ends extending beyond the plaque site.
 9. Anintravascular device according to claim 1, wherein the spikes have alength for piercing into the plaque to a selected depth, and a spacingbetween spikes selected to create desired cleavage lines or planes inthe plaque.
 10. An intravascular device according to claim 9, whereinthe ratio of spacing between spikes to their depth is about 1:1 orgreater.
 11. A method for treating atherosclerotic plaqueintravascularly prior to balloon angioplasty comprising: perforating andserrating the plaque by forming microperforations with lines or patternsof small sharp spikes pressed by expansion to pierce a luminal surfaceof the plaque, wherein the microperforations act as serrations forforming cleavage lines or planes in the plaque that facilitate expansionof the lumen at the plaque site.
 12. A method according to claim 11,which is followed by performing balloon angioplasty to compress theperforation-prepared plaque and enlarge the lumen at a site ofatherosclerotic disease, wherein the perforation preparation enables theballoon angioplasty to be performed with less potential for dissectionand a smoother surface.
 13. A method according to claim 11, wherein theexpansion for pressing the spikes into the plaque is obtained byexpansion of a balloon at a low pressure of about 4 atmospheres or less.14. A method according to claim 13, wherein the expansion of pressingthe spikes is obtained by expansion of the balloon at a very lowpressure of 2 atmospheres or less.
 15. A method according to claim 12,wherein the subsequent balloon angioplasty is performed with adrug-eluting balloon (DEB) or drug-coated balloon (DCB), and thepreparation perforation results in increasing the surface area of theplaque for contact with drug applied during DEB or DCB angioplasty. 16.A method according to claim 12, wherein the subsequent balloonangioplasty is performed at low expansion pressure of 4 atmospheres orless.
 17. A method according to claim 11, wherein the spikes and thedelivery system are also used to transport medication into the plaqueand onto its surface.
 18. A method according to claim 17, wherein thespikes are arranged in one of the following ways consisting of: (i) thespikes have drug-coated tips; (ii) the spikes each have an internaldrug-containing reservoir so that it behaves like a syringe; and (iii)the spikes are detachable from the carrier and are medication-eluting orbearing so that they are detached and left in place after perforation ofthe plaque.
 19. A method according to claim 12, wherein following theballoon angioplasty, any local incidence of post-angioplasty dissectionis treated by applying a thin, ring-shaped tack to retain the plaque atonly the location of the dissection site, rather than applying a stentover the overall plaque site.
 20. A method according to claim 12,wherein following the balloon angioplasty, any incidence ofpost-angioplasty dissection is avoided due to the pre-angioplastypreparation of the plaque by perforation to form cleavage lines orplanes in the plaque and to performing the balloon angioplasty at a lowpressure of about 4 atmospheres or less, thereby avoiding any need forapplying a stent over the plaque site.